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RAS mutations are rare events in Philadelphia chromosome-negative/bcr gene
rearrangement-negative chronic myelogenous leukemia, but are prevalent in
chronic myelomonocytic leukemia
C Hirsch-Ginsberg, AC LeMaistre, H Kantarjian, M Talpaz, A Cork, EJ Freireich, JM Trujillo, MS Lee and SA Stass
Department of Medicine, University of Texas M. D. Anderson Cancer Center,
Houston.
Previous reports have indicated that mutations of the RAS oncogenes are not
associated with the chronic phase of Philadelphia chromosome- positive
chronic myelogenous leukemia (Ph1+ CML). However, further studies were
needed to determine their association with Ph1- CML and chronic
myelomonocytic leukemia (CMML). Therefore, 6 patients with Ph1- CML who
were also negative for BCR rearrangements (Ph1-/BCR- CML) and 30 patients
with CMML were analyzed for the presence of RAS oncogene point mutations to
determine the similarities of these diseases at the molecular level. The
assay used the polymerase chain reaction for amplification of the target
RAS sequences and panels of specific synthetic oligonucleotide probes for
hybridization to wild type and/or mutated sequences. None of the six
Ph1-/BCR- CML patients had mutations in the RAS oncogenes, while 17 of 30
(57%) of the CMML patients had RAS oncogene mutations. Eighty percent of
the mutations involved substitution of aspartic acid for glycine (G----A)
in the 12th or 13th codons of N-ras or K-ras. Furthermore, although not
statistically significant, survival studies raise the possibility of
shortened survival in patients with RAS oncogene point mutations, with the
average survival being 33 months for Ph1-/BCR- CML, 35 months for CMML
without point mutations, and 11 months for CMML with RAS mutations. Thus,
RAS mutations appear to be associated with CMML and not Ph1-/BCR- chronic
phase CML, there is a high propensity for the K-ras or N-ras mutations to
involve an G----A substitution in the 12th or 13th codons, and RAS
mutations in CMML may relate to prognosis and require further studies.
Volume 76,
Issue 6,
pp. 1214-1219,
09/15/1990
Copyright © 1990 by The American Society of Hematology
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